{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPROM1 (also known as CD133) is a pentaspan transmembrane glycoprotein that has emerged as a pivotal marker for both normal stem/progenitor cells and cancer‐initiating cells. Its discovery in multiple tissues has enabled the isolation of small subpopulations with enhanced self‑renewal, differentiation and tumor‐initiating capacities in a wide range of malignancies—including colon, lung, prostate, ovarian, and hepatocellular carcinomas—as well as in sarcomas and gliomas. These PROM1‑expressing cells often display resistance to conventional therapies and are implicated in metastasis and disease recurrence."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its value as a phenotypic marker, PROM1 actively contributes to key molecular processes. In several tumor models, post‐translational modifications of PROM1—such as differential glycosylation affecting the AC133 epitope—and its phosphorylation (for example, at the tyrosine‑828 residue) have been shown to regulate its engagement with intracellular signaling complexes. These modifications mediate direct interactions with components such as the p85 regulatory subunit of phosphoinositide 3‑kinase and HDAC6, thereby stimulating downstream PI3K/Akt and Wnt/β‑catenin pathways that promote survival, proliferation and stemness. In addition, epigenetic events (including alternative promoter usage and DNA methylation) together with environmental stresses like hypoxia or mitochondrial dysfunction have been implicated in modulating PROM1 expression levels."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in stemness and oncogenesis, PROM1 contributes to distinct pathological and therapeutic contexts. Mutations in PROM1 have been directly linked to autosomal‑dominant macular degeneration through mislocalization of the protein and defective photoreceptor disk morphogenesis. Furthermore, PROM1‑positive progenitor cells have been exploited in regenerative applications such as vascular repair and muscle regeneration. Clinically, the prevalence and functional state of PROM1‑expressing cells correlate with tumor invasiveness, chemoresistance and poor patient prognosis, prompting innovative therapeutic strategies—ranging from antibody–drug conjugates to chimeric antigen receptor T cells—to target these cells. These multifaceted functions underscore PROM1’s value not only as a prognostic biomarker but also as a potential therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gavin D Richardson, Craig N Robson, Shona H Lang, et al. 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